Тип публикации: статья из журнала

Год издания: 2024

Идентификатор DOI: 10.1016/j.cell.2024.01.022

Аннотация: Protein structures are essential to understanding cellular processes in molecular detail. While advances in artificial intelligence revealed the tertiary structure of proteins at scale, their quaternary structure remains mostly unknown. We devise a scalable strategy based on AlphaFold2 to predict homo-oligomeric assemblies across fПоказать полностьюour proteomes spanning the tree of life. Our results suggest that approximately 45% of an archaeal proteome and a bacterial proteome and 20% of two eukaryotic proteomes form homomers. Our predictions accurately capture protein homo-oligomerization, recapitulate megadalton complexes, and unveil hundreds of homo-oligomer types, including three confirmed experimentally by structure determination. Integrating these datasets with omics information suggests that a majority of known protein complexes are symmetric. Finally, these datasets provide a structural context for interpreting disease mutations and reveal coiled-coil regions as major enablers of quaternary structure evolution in human. Our strategy is applicable to any organism and provides a comprehensive view of homo-oligomerization in proteomes.

Журнал: Cell

Выпуск журнала: Т. 187, № 4

ISSN журнала: 00928674

Издатель: Cell Press

• Schweke Hugo (Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel)
• Pacesa Martin (Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland)
• Levin Tal (Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel)
• Goverde Casper A. (Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland)
• Kumar Prasun (School of Chemistry, University of Bristol, Bristol BS8 1TS, UK)
• Duhoo Yoan (Protein Production and Structure Characterization Core Facility (PTPSP), School of Life Sciences, École polytechnique Fédérale de Lausanne, Lausanne, Switzerland)
• Dornfeld Lars J. (Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland)
• Dubreuil Benjamin (Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel)
• Georgeon Sandrine (Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland)
• Ovchinnikov Sergey (John Harvard Distinguished Science Fellowship Program, Harvard University, Cambridge, MA, USA)
• Woolfson Derek N. (School of Chemistry, University of Bristol, Bristol BS8 1TS, UK)
• Correia Bruno E. (Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland)
• Dey Sucharita (Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Rajasthan, India)
• Levy Emmanuel D. (Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel)

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